双酚A对高脂饮食小鼠肝损伤与GSK3表达的影响  

Effect of bisphenol A on liver injury and GSK3 expression in mice with high fat diet

作　　者：葛晓蕾 陆晓桐 张小飞 吴明 杜志远 朱启星 沈彤 Ge Xiaolei;Lu Xiaotong;Zhang Xiaofei(Dept of Occupational and Environmol/Lental Health,School of Public Health,Anhui Medical University,Hefei 230032)

机构地区：[1]安徽医科大学公共卫生学院职业卫生与环境卫生学系,合肥230032 [2]安徽医科大学公共卫生学院

出　　处：《安徽医科大学学报》2019年第3期433-438,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81473015;81773467);国家级大学生创新创业训练计划项目(编号:201810366029)

摘　　要：目的研究双酚A(BPA)暴露对高脂饮食(HFD)小鼠肝脏炎性损伤及糖原合成酶激酶3(GSK3)表达的影响。方法 4周龄雄性C57BL/6小鼠用正常饮食(ND)和HFD喂养,分别设置溶剂对照组、10、100和1 000 nmol/L BPA组,经饮水暴露BPA,8周和12周时处死小鼠,取肝脏,HE染色观察肝脏病理变化,免疫组化(IHC)法检测肝脏白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)的表达,Western blot法检测肝脏GSK3α、GSK3α-S21、GSK3β、GSK3β-S9蛋白的表达。结果与ND喂养小鼠比,同一时间点HFD喂养小鼠肝脏炎性细胞浸润增多,TNF-α和IL-1β表达明显增强;ND或HFD喂养小鼠中,肝脏组织病理学变化、TNF-α和IL-1β表达增强呈BPA暴露剂量依赖性,12周时较8周时更显著;与ND喂养小鼠比,HFD喂养的同时间点小鼠肝组织GSK3β-S9和GSK3α-S21表达显著降低(P<0.05);ND或HFD喂养小鼠中,肝组织GSK3β-S9表达降低呈BPA剂量依赖性。结论 BPA暴露可导致小鼠肝脏炎症性损伤,且与HFD具有协同作用,而GSK3β-S9表达降低后上调炎症因子表达在其中发挥重要作用。Objective To explore the effects of bisphenol A(BPA)exposure on liver injury and glycogen synthase kinase 3(GSK3)expression in high fat diet-fed mice.Methods Four-week-old male C57BL/6 mice were fed with normal diet(ND)and high fat diet(HFD),and divided into solvent control group,10 nmol/L BPA,100 nmol/L BPA and 1 000 nmol/L BPA groups.The mice were exposed to BPA by drinking water.Eight weeks and 12 weeks after administered,the mice were killed.The liver of the mice was taken and the pathological changes of the liver were observed by H&E staining.The expression of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the liver was detected by immunohistochemistry(IHC).The expression of GSK3α,GSK3α-S21,GSK3β,GSK3β-S9 protein in the liver was detected by Western blot.Results Compared with ND-fed mice,infiltration of inflammatory cells and TNF-α,IL-1βexpression at the same time point were increased significantly in liver tissue of HFD-fed mice.In the mice fed with ND or HFD,the histopathological changes of liver and the increased expression of TNF-αand IL-1βin liver were dose-dependent on BPA exposure.Those of 12 weeks were more significantly than those of 8 weeks.Compared with ND-fed mice,at the same time point,the expression of GSK3β-S9 and GSK3α-S21 in liver were significantly decreased in mice fed with HFD(P<0.05).In the mice fed with ND or HFD,the decreased expression of GSK3β-S9 in the liver were dose-dependent on BPA exposure(P<0.05).Conclusion Exposure to BPA can cause inflammatory injury in the liver of mice,and has a synergistic effect with HFD,and decreased expressions of GSK3β-S9 may play an important role in it by up-regulating the expression of inflammatory factors.

关 键 词：双酚A 糖原合成酶激酶3 肝脏 炎症损伤 

分 类 号：Q591.1[生物学—生物化学] R994.6[医药卫生—毒理学]